Albanese C, Colin I M, Crowley W F, Ito M, Pestell R G, Weiss J, Jameson J L
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Recent Prog Horm Res. 1996;51:23-58; discussion 59-61.
The glycoprotein hormones (TSH, FSH, LH, CG) are structurally related proteins with diverse physiologic functions. This family of hormones offers an opportunity to address fundamental questions concerning how gene expression is regulated in a cell-specific manner and in response to different hormones. For example, the alpha-subunit gene is expressed in several different pituitary cell types (gonadotropes and thyrotropes) as well as in the placenta. Because it must be coordinantly expressed with the different beta-subunit genes, the alpha-gene provides an interesting model for multihormonal control which varies in a cell-type specific manner. Many of the promoter regulatory DNA sequences and cognate transcription factors in the alpha-gene have been identified. These studies reveal a remarkable series of composite regulatory elements that interact with families of transcription factors that are still being characterized. In contrast, the beta-subunit genes are notable for restricted cell-type expression and more limited hormonal regulation that reflects their individual physiologic roles. The TSH beta gene is expressed only in thyrotropes where, in conjunction with the alpha-gene, it is subject to transcriptional repression by thyroid hormone. The FSH beta gene is expressed in gonadotropes where its expression is controlled primarily by activin and inhibin, with additional regulation by GnRH. The LH beta gene is also expressed in gonadotropes, but it is more dependent upon GnRH input and its expression is unaffected by the activin/inhibin system. The CG beta gene evolved recently from the LH beta gene and in the process, the CG beta promoter acquired new regulatory elements that favor its expression in the placenta rather than the pituitary gland. Less is known about the regulatory elements in the beta genes, in part because highly differentiated cells are required for their normal regulation. This chapter reviews the regulation of this family of genes with an emphasis on recent studies from our laboratory involving the gonadotropins (LH, FSH, CG). Concomitant with our advancing understanding of how the gonadotropin genes are regulated, we are also learning about genetic causes of gonadotropin deficiency syndromes.
糖蛋白激素（促甲状腺激素、促卵泡激素、促黄体生成素、绒毛膜促性腺激素）是结构相关的蛋白质，具有多种生理功能。这个激素家族为解决有关基因表达如何以细胞特异性方式以及如何响应不同激素进行调控的基本问题提供了契机。例如，α亚基基因在几种不同的垂体细胞类型（促性腺激素细胞和促甲状腺激素细胞）以及胎盘中表达。由于它必须与不同的β亚基基因协调表达，α基因提供了一个有趣的多激素调控模型，该模型以细胞类型特异性方式变化。α基因中的许多启动子调控DNA序列和同源转录因子已被确定。这些研究揭示了一系列与仍在表征的转录因子家族相互作用的复合调控元件。相比之下，β亚基基因以其受限细胞类型表达和反映其各自生理作用的更有限激素调控而著称。促甲状腺激素β基因仅在促甲状腺激素细胞中表达，在那里它与α基因一起受到甲状腺激素的转录抑制。促卵泡激素β基因在促性腺激素细胞中表达，其表达主要受激活素和抑制素控制，同时受促性腺激素释放激素的额外调控。促黄体生成素β基因也在促性腺激素细胞中表达，但它更依赖促性腺激素释放激素的输入，其表达不受激活素/抑制素系统影响。绒毛膜促性腺激素β基因最近从促黄体生成素β基因进化而来，在此过程中，绒毛膜促性腺激素β启动子获得了有利于其在胎盘而非垂体中表达的新调控元件。关于β基因中的调控元件了解较少，部分原因是其正常调控需要高度分化的细胞。本章综述了这个基因家族的调控，重点是我们实验室最近关于促性腺激素（促黄体生成素、促卵泡激素、绒毛膜促性腺激素）的研究。随着我们对促性腺激素基因调控方式的深入理解，我们也在了解促性腺激素缺乏综合征的遗传原因。
